Summit Therapeutics - Q2 2024
August 6, 2024
Transcript
Operator (participant)
Good morning, and welcome to Summit Therapeutics' Second Quarter 2024 Earnings and Update Call. All participants will be in listen-only mode until the question-and-answer portion of this call. We do not expect any technical difficulties today. However, in the event that we lose the webcast connection and are unable to provide any updates, please wait up to 10 minutes for resolution. Please refer to the company's website for updates, and please note that today's call is being recorded. If you would like to ask a question during the Q&A session, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question at any time, you can press star one again. At this time, I would like to turn the call over to Dave Gancarz, Summit Therapeutics' Chief Business and Strategy Officer. You may proceed.
Dave Gancarz (Chief Business and Strategy Officer)
Good morning, and thank you for joining us. Our press release was issued earlier this morning and is available on the homepage of our website. Our Form 10-Q was also filed earlier this morning and is available on our website. Today's call is being simultaneously webcast, and an archive replay will also be made available later today on our website, www.smttx.com. Joining me on the call today is Bob Duggan, our Chairman of the Board and Chief Executive Officer, Dr. Maky Zanganeh, our Chief Executive Officer and President, Manmeet Soni, our Chief Operating Officer and Chief Financial Officer, and Dr. Allen Yang, our Chief Medical Officer. Before we get started with the rest of the call, I would like to note that some statements made by our management team and some responses to questions that we may make today may be considered forward-looking statements based on our current expectations.
Summit cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Please refer to our SEC filings for information about these risks and uncertainties. Summit undertakes no obligation to update these forward-looking statements except as required by law. Following comments from Bob, Maky, and Manmeet, we will take questions. With that, I would like to turn the call over to Bob.
Bob Duggan (Chairman and CEO)
Thank you, Dave. Good morning, everyone, and thank you for joining us today. We're very proud of the recent accomplishments of Team Summit and the expanding positive information that continues to be brought to light surrounding ivonescimab, our lead investigational asset. The past few months have been pivotal to the positive development and awareness of ivonescimab, as well as in expanding physician, caretaker, hospital, payer, and patient awareness of Summit Therapeutics' mission and vision. Namely, to build a viable organization that makes a significant positive difference for the betterment of patients encountering serious unmet oncology medical needs. Specifically, ivonescimab created positive phase III data updates from HARMONi-A and HARMONi-2, both of which were randomized, single-region clinical trials in non-small cell lung cancer conducted by our partners at Akeso.
HARMONi-A results supported ivonescimab receiving its first regulatory approval in China for patients with advanced non-small cell lung cancer who have progressed following an EGFR TKI. In HARMONi-2, ivonescimab monotherapy beat pembrolizumab monotherapy head-to-head in the study's primary endpoint of PFS, making ivonescimab the first drug to achieve a clinically meaningful efficacy benefit over pembrolizumab in a randomized phase III clinical trial in non-small cell lung cancer. Additional data from this pre-specified interim analysis will be presented at an upcoming major medical conference this quarter. In addition, we raised an unsolicited $200 million at a premium over the then current market price, extending our cash runway and increasing our resources to execute our expansive goals. Manmeet will provide more details about our financial position in a few minutes. Summit's two multi-regional registrational phase III non-small cell lung cancer trials, HARMONi and HARMONi-3, continue to enroll.
HARMONi remains on track to complete its planned enrollment later this year. Alongside our partners at Akeso, ivonescimab data was featured at ASCO, as well as HARMONi-A data being published in JAMA, Journal of the American Medical Association. This, in addition to smaller conferences and Best of ASCO follow-up meetings, have been excellent in fostering KOL discussions regarding the future of cancer therapy, including the potential for ivonescimab. These efforts were further bolstered as we continued to ramp our investigator-sponsored trial or IST program. Last month, we announced a five-year strategic collaboration with MD Anderson to accelerate development of ivonescimab through the opportunity to conduct multiple clinical trials with one of the world's most respected medical healthcare institutions.
These efforts are in addition to our continued collaboration with our partners at Akeso, who continue to generate patient-positive data in phase II settings in both lung cancer and solid tumors outside of lung cancer, data which can help support additional late-stage clinical trials. These accomplishments have been foundational to our 2024 goals of successfully executing on our registrational phase III trials while expanding our clinical development program. Maky will further expound upon these accomplishments, including additional strides we have made to drive our firm continued belief and conviction in Team Summit and the potential of ivonescimab in non-small cell lung cancer and beyond. We are an experienced, mission-driven organization with a collective goal to improve quality of life, increase potential duration of life, and resolve serious unmet medical needs.... We believe we have the right team and the right molecule in ivonescimab to help us realize this goal.
With that, I will turn the call over to Maky for additional context and recent highlights for consideration.
Maky Zanganeh (CEO and President)
Thank you, Bob, and good morning, everyone. As Bob mentioned, I remain incredibly enthusiastic about the accomplishments of Team Summit and our partnership with Akeso. Before touching on the clinical highlights of ivonescimab, I would like to speak to the expansive clinical development work we have conducted with ivonescimab. Between Summit and Akeso, over 1,800 patients have been treated with ivonescimab in clinical studies to date worldwide. There have been 20 clinical trials around the globe evaluating ivonescimab. While our phase III programs across Summit and Akeso are currently focused in non-small cell lung cancer, seven of the clinical trials for ivonescimab are evaluating our lead candidate in solid tumor settings beyond non-small cell lung cancer. Of course, we are sponsoring two clinical trials, both of which are phase III studies, HARMONi and HARMONi-3.
As a reminder, ivonescimab is the only PD-1 VEGF bispecific antibody in phase III in our licensed territories. ivonescimab brings these two highly validated mechanism of action together into one novel molecule, targeting simultaneously both PD-1 and VEGF. Next, I would like to review our recent achievements as well as touch on some upcoming catalysts for the remainder of this year. As a reminder, our partnership with Akeso became effective at the beginning of 2023. At the time, Akeso was enrolling or completing enrollment in two phase III clinical trials. We immediately got to work and enrolled our first patient in HARMONi in the first half of 2023, began HARMONi-3 enrollment in the fourth quarter of 2023, and helped to ensure ivonescimab was featured at several medical conferences.
The second quarter of 2024 was a pivotal moment for our ivonescimab and its development, with two major catalyst events occurring around the time of the ASCO 2024 conference. Ivonescimab received marketing approval in China, supported by Akeso HARMONi-A Phase III clinical trial for patients with advanced non-small cell lung cancer who progressed following an EGFR TKI. This data was subsequently featured in an oral presentation at ASCO, and the HARMONi-A study was published in the Journal of the American Medical Association, or JAMA. We also announced that HARMONi-2 met its primary endpoint of progression-free survival in pre-specified interim analysis, in which ivonescimab monotherapy in a head-to-head trial against pembrolizumab monotherapy achieved a statistically significant and clinically meaningful benefit in patients in China with first-line non-small cell lung cancer whose tumors were positive for PD-L1 expression.
Improvement in PFS was observed broadly across subgroups, including PD-L1 low and PD-L1 high-expressing tumors, as well as squamous and non-squamous histologies. We look forward to having additional HARMONi-2 data presented at a major medical conference this quarter. Looking to the remainder of 2024, in addition to the HARMONi-2 data read-out, we plan to complete enrollment in our multi-regional HARMONi trial later this year and expect additional phase II data in lung and non-lung indications to be presented at multiple medical conferences in the upcoming months, including the World Conference on Lung Cancer and ESMO. ESMO recently released abstract titles featuring ivonescimab in phase II studies in triple-negative breast cancer, colorectal cancer, and head and neck cancer.
We are fortunate to have created such a strong partnership in our ongoing collaboration with Akeso as we leverage data from multiple solid tumor studies, supporting and informing Summit's own late-stage clinical development strategy in our licensed territories. With meaningful updates from Akeso HARMONi-A and HARMONi-2 occurring this past quarter, we wanted to take the opportunity on this quarter's earnings call to review both phase III study design and highlight some key results. Starting with HARMONi-A, this is a double-blinded, placebo-controlled, single-region randomized phase III trial evaluating ivonescimab plus chemotherapy versus placebo plus chemotherapy for patients with advanced or metastatic EGFR mutant non-small cell lung cancer and disease progression after EGFR TKI treatment. 322 patients were enrolled across 55 study sites in China, and patients were stratified for exposure to third-generation EGFR TKI treatment and the presence of brain metastasis.
As a reminder, approximately 85% of HARMONi-A patients are intended to be included in our own HARMONi study analysis, representing those patients in HARMONi-A who received a third-generation EGFR TKI prior to entering the trial. In HARMONi-A, the primary endpoint of progression-free survival per Independent Radiologic Review Committee was met, achieving a PFS hazard ratio of 0.46, representing a 54% reduction in the risk of disease progression or death compared to chemotherapy. Additionally, the subgroup of patients receiving a third-generation EGFR TKI, like osimertinib, experienced a reduced risk of disease progression or death of 52% or a hazard ratio of 0.48, as our HARMONi trial enrollment is expected to complete in the second half of this year. We remain strongly encouraged by the opportunity for ivonescimab.
In addition, an overall survival analysis of the HARMONi-A data was requested by the Chinese Regulatory Authority as a part of its review of ivonescimab for marketing approval in China, at 52% data maturity, median overall survival in the ivonescimab arm showed a positive survival trend with a hazard ratio of 0.80. ivonescimab was well tolerated and demonstrated a manageable safety profile. Treatment-related adverse events leading to discontinuation were 5.6% in the treatment arm, compared to 2.5% in the placebo arm, and there were no deaths reported in either arm. Grade three or higher immune-related adverse events were reported in 6.2% of patients in the treatment arm versus 2.5% of patients in the placebo arm.
Grade three or higher potential VEGF-related adverse events were reported in 3.1% of patients in the treatment arm versus 2.5% of patients in the placebo arm. There were no Grade three or higher bleeding events observed in either arm. Moving to HARMONi-2, this Akeso-sponsored study in a single-region, multicenter, double-blinded, randomized, phase III trial evaluating monotherapy ivonescimab head-to-head against monotherapy pembrolizumab as first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer, whose tumors have positive PD-L1 expression or a TPS score of greater than 1%. Patients in the study are stratified by PD-L1 low or TPS scores of 1%-49% and PD-L1 high or TPS score of 50% or greater, squamous versus non-squamous histology, and stage of disease. HARMONi-2 primary endpoint is progression-free survival as measured by independent radiologic review committee.
In high-level results for HARMONi-2, ivonescimab demonstrated statistically significant, clinically meaningful improvement in progression-free survival over pembrolizumab. This benefit was observed across patient subgroups, including PD-L1 low, PD-L1 high, squamous and non-squamous histologies, as well as other high-risk patients. Notably, no other randomized Phase III clinical trials in non-small cell lung cancer have demonstrated a statistically significant improvement in progression-free survival in head-to-head setting versus pembrolizumab. As mentioned previously, we are eager to share more information when the HARMONi-2 interim analysis data set is presented at an upcoming major medical conference this quarter. The PD-L1 subgroups, as well as the subgroups by histology, are important in terms of informing next steps in our clinical development pathway for indication both within lung and beyond lung.
We had many highlights this past quarter and touched on most of them already, but would like to mention our five-year strategic collaboration with the MD Anderson Cancer Center that was announced last month, in which the development of ivonescimab will be accelerated in several solid tumor types across multiple studies. MD Anderson will lead these clinical trials to evaluate the safety and potential clinical benefit of ivonescimab, including the possibility of identifying biomarkers through additional research activities. Early work may include renal cell carcinoma, colorectal cancer, skin cancer, breast cancer, and glioblastoma. The partnership has the potential to rapidly expand ivonescimab's development program. We expanded our licensed territories to include Latin America, including Mexico and all countries in Central America, South America and the Caribbean, the Middle East, and Africa. In addition to our original licensed territories, which include the U.S., Europe, Canada, and Japan.
We are excited to expand upon our existing territories as we seek to bring ivonescimab to as many people around the globe as possible. In addition, I would like to take a moment to acknowledge that we strengthened our greater team recently with two new appointments to our board of directors. In April 2024, renowned executive and genomicist, Dr. Mostafa Ronaghi, joined our board. He has played a leading role in the development of technology, which have helped improve the odds for patients with cancer, including biomarker-driven diagnostics, such as next-generation sequencing technology and platforms. He has co-founded several companies, as well as being Illumina's Chief Technology Officer from 2008 to 2021. In June, Mr. Jeff Huber, the transformational Google and GRAIL executive, joined our board as well.
Prior to his current role leading Triatomic Capital, a VC firm, Jeff was the founding CEO and vice chairman of GRAIL, a mission-driven company seeking to detect cancer early when it can be cured. Prior to GRAIL, he was a Senior Vice President at Alphabet Inc, formerly known as Google Inc. Over 30 years at Google, he co-founded Google's life sciences effort in Google X, and he led development and scaling of Google Maps, Google Apps, such as Gmail, Google Calendar, Google Docs, as well as Google Ads. Jeff managed a team of over 5,000 employees and five billion P&L during his time at Google. In addition, Jeff is also a board member at several other cutting-edge companies.
We are fortunate to have Mostafa and Jeff's perspectives and expertise as they join us in our mission to make a significant positive difference in the lives of patients with serious unmet medical needs. Finally, I would like to take a moment to thank Team Summit. As Bob and I have described all of the accomplishments we have achieved over the past year and a half with ivonescimab, this team has done a remarkable job across every team in making our goals a reality. It is tremendous honor and privilege to work with each member of Team Summit, and I would like to express my heartfelt thanks to each and every one of our great team members. With that update, I will now ask Manmeet to provide details on our financial position and outlook. Manmeet?
Manmeet Soni (COO and CFO)
Thank you, Maky, and good morning, everyone. We filed this morning our 10-Q for the second quarter of 2024. Today, I will provide you with an update on three items: our cash position after our recent $200 million financing, our updated cash runway guidance, and second quarter operating expenses. Let me start with cash position. We ended the second quarter of 2024 with a cash position of $325.8 million. This cash position was strengthened at the end of second quarter with the closing of a $200 million unsolicited private placement from a single institutional investor in June 2024. This morning, we also filed a Form S-3 in order to register the shares, which were issued in the private placement on June 6th, 2024.
Moving to updated cash runway guidance, based on our planned operations, including our two phase II clinical trials, we updated our cash runway guidance and now expect that we have sufficient cash to run our operations into fourth quarter of 2025. Turning to operating expenses, I'll provide details to both GAAP and non-GAAP numbers. You can refer to our press release issued this morning for a reconciliation of GAAP to non-GAAP financial measures. Non-GAAP expenses exclude stock-based compensation and one-time charges related to acquired in-process R&D expenses. Our GAAP R&D expenses during the second quarter were $30.8 million, compared to $30.9 million for the first quarter of 2024. Non-GAAP R&D expenses were $27.3 million in the second quarter of 2024, compared to $28.5 million for the first quarter of 2024.
Our GAAP acquired IP R&D expenses during the second quarter were $15 million, compared to 0 for the first quarter of 2024. This $15 million expense is related to our upfront consideration for adding territories of Latin America, Africa, and Middle East as per the June 2024 license agreement amendment with Akeso. Turning to G&A, GAAP G&A expenses for our second quarter of 2024 totaled $14 million, compared to $11.7 million for the first quarter of 2024. Non-GAAP G&A expenses were $6.4 million during the second quarter of 2024, compared to $4.6 million for the first quarter of 2024. Overall, our non-GAAP operating expenses during second quarter 2024 were $33.7 million, consistent with $33.1 million for the first quarter of 2024.
With that, I will hand it back over to Dave.
Dave Gancarz (Chief Business and Strategy Officer)
Thank you, Bob, Maky, and Manmeet. We'll now see if there are any questions that our team can help answer. Christina, if you could please open the line for questions.
Operator (participant)
Yes, thank you. And at this time, I'd like to remind everyone, in order to ask a question, please press star, then the number one on your telephone keypad. Again, please press star one to ask a question. We'll pause for a moment to compile the Q&A roster. And your first question comes from the line of Brad Canino from Stifel. Your line is open.
Dara Azar (Biotech Equity Research Analyst)
Great. Thanks for taking our question. This is Dara Azar on for Brad. Could you be able to walk through the puts and takes of data disclosure if HARMONi-2 is at World Lung? When is the title announced, or things like, should we expect an abstract text before the presentation to have a lifted embargo? And if so, what data could be included in the abstract?
Dave Gancarz (Chief Business and Strategy Officer)
Sure. Thanks, Dara. I appreciate the question. This is Dave responding. So, as you can imagine, our HARMONi-2 data is considered a late breaker abstract at the World Conference on Lung Cancer or World Lung. So our partners at Akeso previously announced their intention to submit the HARMONi-2 data to the World Lung Conference. So the deadline for abstracts for World Lung were July 31st. Notifications to the primary authors of each of those abstracts that are late breakers are provided early in August, but generally between the 7th and the 10th of August. Traditionally, our understanding of what World Lung does is around August 15th, releases the titles and abstracts from most of the remaining.
So they've released some of the original, titles already, but for the remaining, titles and abstracts released around, August 15th. However, what they do is they, withhold the number of what they consider Presidential Symposium, or otherwise larger presentations until the actual conference itself, at which point they only release the title, but, but the abstract is held until, the conference itself. So at this point, because we haven't yet, technically hit the acceptance time period of August seventh to tenth, we're not, yet made aware in terms of whether our abstract will be held back or not. So Dara, I appreciate the question. It's a very good question in terms of exactly the timeline of when things will come up.
But until we hit the approval date from World Lung between the 7th and 10th of August, and then they announce what they will and won't hold back until the conference itself, you know, we'll need to wait patiently alongside you in terms of those details.
Dara Azar (Biotech Equity Research Analyst)
Yeah, very helpful overview. If I may ask a follow-up, what is your latest view on OS maturity? If it's going to be mature enough to, for inclusion in the presentation. If not, would the, you know, would there be any language in the, abstract to describe the trend observed? And if there's time, I'll come back for another follow-up.
Dave Gancarz (Chief Business and Strategy Officer)
... Sure, Dara. So, I, this is Dave again. I'll start, and then I'll let Allen add any additional context that he'd like to. But if you recall, from the earlier trials that were run with pembrolizumab as a monotherapy in the setting, the Keynote-024 and the Keynote-042 settings. There was the time period by which they reached their survival maturity was a little bit longer than the time period in which this trial has matured from last patient in. So as a reminder, HARMONi-2 completed enrollment around the end of the third quarter, beginning of the fourth quarter of 2023. And so as that interim analysis was run, and ultimately the IDMC met, and then we released the top line data along with our partners at Akeso in May.
Not a lot of time from an overall survival perspective had transpired from when the trial completed enrollment. And so as a result, anything that we have at this point will be early. So we haven't made definitive announcements or decisions on exactly what will be presented with respect to overall survival. But what I would say is, it's, we're not holding anything back at this point, as much as time needs to take place for these patients to remain on trial and study to get a mature enough readout for overall survival at a mature level.
Allen Yang (CMO)
Yeah, not much to add, Dave, except that it is very early in this study. Remember, they just completed enrollment. This study hit its first primary or interim analysis very early, so the data were very immature, at the time, and I think that goes to the strength of the PFS data to date.
Dara Azar (Biotech Equity Research Analyst)
Yeah. Thank you. Makes a lot of sense. And as a last two-parter, without OS, how do you think about what constitutes a, you know, good PFS result in isolation? And finally, how should we be thinking about additional phase III plans, perhaps announcement in relation to HARMONi-2, medical meeting update? That's it from me. Thank you.
Allen Yang (CMO)
Yeah. So I'll take the first question. In terms of the PFS, we're not gonna comment on that. You know, you'll have to come see us at that meeting, and then you'll see the results there. And I understand why everybody's interested in that. We're just not gonna disclose it at this time. In terms of additional phase III programs, you probably won't make announcements at World Lung, but you'll see some data maturing in lungs and some other lung indications as well. And the development plan will be fairly obvious in terms of recreating sort of key studies that Merck or AstraZeneca has done in the past, and we'll probably prioritize based on that need.
Dara Azar (Biotech Equity Research Analyst)
Thank you.
Operator (participant)
Sir. Okay, great. Thank you. And your next question comes from the line of Yigal Nochomovitz from Citigroup. Your line is open.
Yigal Nochomovitz (Director of Biotech Equity Research)
Hi. Great, thanks so much for taking the question. Obviously, a very key one for investors, and I've received a lot of questions on, is the, the read-through from HARMONi-2 to HARMONi-3. So I'm curious, given the, the apparent strength of the PFS data in HARMONi-2, could you comment as to how you're thinking about the addition of the chemo backbone in terms of, extracting the relative benefit of ivonescimab over Keytruda in squamous, in HARMONi-3? And I have a few follow-ups. Thanks.
Allen Yang (CMO)
Yeah, Yigal. Thanks for the question. So, you know, we're very confident for HARMONi-3. I think the strength of the HARMONi-2 data has given us more confidence. I mean, remember, we decided to do HARMONi-3 before the HARMONi-2 data were available. So we thought that squamous was an unmet need. We thought that VEGF-targeted agents were never developed in squamous because of safety concerns. We did not see those safety concerns in the development of ivonescimab, and that's why we thought HARMONi-3 was low-hanging fruit for ivonescimab. Given the strength of the HARMONi-2 data, we're even more confident. You know, the addition of chemotherapy may change things in terms of, you know, reduction to tumors, but I don't think it'll change biologically the importance of ivonescimab for this, for this population. And then the second question was on...
Dave Gancarz (Chief Business and Strategy Officer)
Sorry, Yigal, could you repeat the second question?
Yigal Nochomovitz (Director of Biotech Equity Research)
I didn't ask it yet. The second one was, the second one was just to confirm. So for HARMONi-2, it's TPS greater than 1%. For HARMONi-3, is it all TPS scores, and does that make any notable difference in your mind, or not really?
Allen Yang (CMO)
Yeah, it's for all TPS scores, and it did. You know, going into this study in terms of the HARMONi-3, before we had the HARMONi-2 results, I was actually more confident in the lower TPS expressing or the lower PD-L1-expressing patients because of the VEGF component. But looking at the HARMONi-2 data, as we said publicly, we seem to see a benefit across PD-L1 expression levels. So it—we don't think it matters what patients will come onto the study.
Yigal Nochomovitz (Director of Biotech Equity Research)
Okay. Another key question in terms of the catalyst path for the company is potential interim readouts for HARMONi 3, and I understand they're built into the protocol. Could you comment at all as to what might be in store as far as potential interim readouts for HARMONi 3 over the next several quarters? Thanks.
Allen Yang (CMO)
Yeah, Yigal, that, that's a great question, and we can't really disclose that, and we haven't disclosed that at this time. I will say that our Akeso partners are running a parallel study called the 306 study, which is actually in the same, a similar population, which is ivonescimab against, tislelizumab, which is the standard of care in China. So those results won't be out, earlier as well, but we haven't disclosed, nor has our Akeso partner disclosed any timelines around that.
Yigal Nochomovitz (Director of Biotech Equity Research)
Okay. And then the last question is, I think, Maky mentioned that there were some abstract titles for some of these other solid tumors in phase II, triple negative breast, colorectal, head and neck. But then you also are starting the MD Anderson partnership. So can you just kind of comment on how those two work streams are gonna intersect between your own phase II work, as well as what MD Anderson is doing with respect to tumors outside of lung?
Allen Yang (CMO)
... Hey, Yigal, thanks for the question. Yeah, so first of all, the MD Anderson collaboration is very exciting. You know, speaking with physicians and experts at MD Anderson gives us access to, you know, a treasure trove of scientific and clinical expertise. I think if you look at the way the two programs interact, remember Akeso is doing a lion's share of the phase II work, and they've done quite a lot of phase II work. However, there might be some minor gaps in the sense that the standard care in China is different or certain tumor types are not as prevalent in China, and this is where MD Anderson can help us get quick signals, some phase II data as well. And then again, the scientific expertise.
So when we have a question around a certain tumor type or certain subsets of tumor types that they're not interested in China, this is where the gap will be filled with MD Anderson. Without specific questions. Do you have specific questions on specific tumor types?
Yigal Nochomovitz (Director of Biotech Equity Research)
No, not at this point, but that's helpful.
Allen Yang (CMO)
Yeah.
Yigal Nochomovitz (Director of Biotech Equity Research)
Thank you.
Allen Yang (CMO)
Yeah, yeah. Thanks, Yigal.
Dave Gancarz (Chief Business and Strategy Officer)
Thanks, Yigal.
Operator (participant)
Your next question comes from the line of Mitchell Kapoor from H.C. Wainwright. Your line is open.
Mitchell Kapoor (Director and Senior Biotechnology Analyst)
Everyone, thanks for taking our questions, and congrats on the recent data. The first question I have here is, just given the fact that most of the 420 HARMONi patients will be bundled from HARMONi-A, would you potentially envision something similar for leveraging the HARMONi-2 data in the US?
Allen Yang (CMO)
Possibly, and so we're in the midst of negotiations, sort of discussions with the agency. It's clear that we won't be able to file on the HARMONi-2 data in all regions, and so that's something that we're gonna try to address. However, there is an opportunity to leverage the HARMONi-2 data in future studies as well, without disclosing more than that.
Mitchell Kapoor (Director and Senior Biotechnology Analyst)
Okay, great. Thank you. And then, just broadly on the use of ivonescimab in lower PD-L1 TPS scores, thinking like closer to one versus the 49 range, is there a threshold where ivonescimab becomes more clearly effective?
Allen Yang (CMO)
Yeah. Well, so I think the best data results are from the 201 and the 202 study, the phase II data. And you see a clear trend where the response rate does increase as PD-L1 expression increases. And in the opposite direction, as PD-L1 expression decreases, the level of activity drops off, but not as sharply as other PD-1 or PD-L1 agents. So I think this is probably the VEGF effect. And, you know, there are other bispecific immunotherapies out there, like PD-1 CTLA-4, that are looking at the PD-1 negatives. So the question is, how good will we be there? And I think we'll be pretty strong there as well. So I get the question. We see the benefit across the whole spectrum. The benefit seems to be greater in the high PD-1.
Relative to PD-1s, where is that relative benefit? The relative benefit is actually greater, even though the overall response rate is a little bit lower in the low PD-L1 expression. I know that's kind of confusing, but again, I think we see good activity across all PD-L1 expressions. There's a slight increase for ivonescimab for the PD-1s, high expression, PD-L1 high expressions as well.
Dave Gancarz (Chief Business and Strategy Officer)
As a reference point, this is Dave, Mitchell, that you can go back to, is the ASCO 2023 poster, which actually kind of lays out, by PD-L1 expression status, in the phase II trials, as Allen mentioned, especially in combination with chemo, the relative benefit in the by PD-L1 expression.
Mitchell Kapoor (Director and Senior Biotechnology Analyst)
Great. Thank you, Dave and Allen. Really, really appreciate it. It makes a lot of sense.
Operator (participant)
Thank you. Once again, if you do have a question, please press star one on your telephone keypad. Again, if you do have a question, please press star one. Thank you. With no further questions, Dave, I'll turn the floor back over to you.
Dave Gancarz (Chief Business and Strategy Officer)
Thank you very much. We appreciate everyone taking the time to join us this morning for our quarterly earnings call. We appreciate your continued support, and we wish you a great day. Thank you very much.
Operator (participant)
Thank you. Once again, this does conclude today's conference call. You may now disconnect. Have a great day.